Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of ...N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.
Perceptual success depends on fast-spiking, parvalbumin-positive interneurons (FS/PVs). However, competing theories of optimal rate and correlation in pyramidal (PYR) firing make opposing predictions ...regarding the underlying FS/PV dynamics. We addressed this with population calcium imaging of FS/PVs and putative PYR neurons during threshold detection. In primary somatosensory and visual neocortex, a distinct PYR subset shows increased rate and spike-count correlations on detected trials (“hits”), while most show no rate change and decreased correlations. A larger fraction of FS/PVs predicts hits with either rate increases or decreases. Using computational modeling, we found that inhibitory imbalance, created by excitatory “feedback” and interactions between FS/PV pools, can account for the data. Rate-decreasing FS/PVs increase rate and correlation in a PYR subset, while rate-increasing FS/PVs reduce correlations and offset enhanced excitation in PYR neurons. These findings indicate that selection of informative PYR ensembles, through transient inhibitory imbalance, is a common motif of optimal neocortical processing.
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•>40% of PV+ inhibitory neurons predict perception with increased or decreased rate•Correlations increase among predictive pyramidal ensembles on successful trials•Modeling suggests enhanced feedback to rate-increasing interneurons drives imbalance•Selection of informative ensembles via inhibitory imbalance may be a common motif
Deister et al. study how rate and correlation changes among neocortical excitatory and inhibitory neurons predict perceptual success. Neurons with predictive rate changes show increased correlations. Neurons without predictive rate changes have decreased correlations. They propose a potential circuit motif where similar sensory, but variable contextual, inputs drive inhibitory imbalances and recruitment of distinct ensembles.
Beta oscillations (15-29Hz) are among the most prominent signatures of brain activity. Beta power is predictive of healthy and abnormal behaviors, including perception, attention and motor action. In ...non-averaged signals, beta can emerge as transient high-power 'events'. As such, functionally relevant differences in averaged power across time and trials can reflect changes in event number, power, duration, and/or frequency span. We show that functionally relevant differences in averaged beta power in primary somatosensory neocortex reflect a difference in the number of high-power beta events per trial, i.e. event rate. Further, beta events occurring close to the stimulus were more likely to impair perception. These results are consistent across detection and attention tasks in human magnetoencephalography, and in local field potentials from mice performing a detection task. These results imply that an increased propensity of beta events predicts the failure to effectively transmit information through specific neocortical representations.
The rare-earth peak in the r-process abundance pattern depends sensitively on both the astrophysical conditions and subtle changes in nuclear structure in the region. This work takes an important ...step towards elucidating the nuclear structure and reducing the uncertainties in r-process calculations via precise atomic mass measurements at the JYFLTRAP double Penning trap. ^{158}Nd, ^{160}Pm, ^{162}Sm, and ^{164-166}Gd have been measured for the first time, and the precisions for ^{156}Nd, ^{158}Pm, ^{162,163}Eu, ^{163}Gd, and ^{164}Tb have been improved considerably. Nuclear structure has been probed via two-neutron separation energies S_{2n} and neutron pairing energy metrics D_{n}. The data do not support the existence of a subshell closure at N=100. Neutron pairing has been found to be weaker than predicted by theoretical mass models. The impact on the calculated r-process abundances has been studied. Substantial changes resulting in a smoother abundance distribution and a better agreement with the solar r-process abundances are observed.
Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely ...understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B
mouse model of ASD. Male and female Shank3B
mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task. In vivo population calcium imaging in vibrissa primary somatosensory cortex (vS1) revealed increased spontaneous and stimulus-evoked firing in pyramidal neurons but reduced activity in interneurons. Preferential deletion of Shank3 in vS1 inhibitory interneurons led to pyramidal neuron hyperactivity and increased stimulus sensitivity in the vibrissa motion detection task. These findings provide evidence that cortical GABAergic interneuron dysfunction plays a key role in sensory hyper-reactivity in a Shank3 mouse model of ASD and identify a potential cellular target for exploring therapeutic interventions.
The McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, the Massachusetts Institute of Technology, Cambridge, Massachusetts
ABSTRACT
Brain vasculature is a complex ...and interconnected network under tight regulatory control that exists in intimate communication with neurons and glia. Typically, hemodynamics are considered to exclusively serve as a metabolic support system. In contrast to this canonical view, we propose that hemodynamics also play a role in information processing through modulation of neural activity. Functional hyperemia, the basis of the functional MRI (fMRI) BOLD signal, is a localized influx of blood correlated with neural activity levels. Functional hyperemia is considered by many to be excessive from a metabolic standpoint, but may be appropriate if interpreted as having an activity-dependent neuro-modulatory function. Hemodynamics may impact neural activity through direct and indirect mechanisms. Direct mechanisms include delivery of diffusible blood-borne messengers and mechanical and thermal modulation of neural activity. Indirect mechanisms are proposed to act through hemodynamic modulation of astrocytes, which can in turn regulate neural activity. These hemo-neural mechanisms should alter the information processing capacity of active local neural networks. Here, we focus on analysis of neocortical sensory processing. We predict that hemodynamics alter the gain of local cortical circuits, modulating the detection and discrimination of sensory stimuli. This novel view of information processing—that includes hemodynamics as an active and significant participant—has implications for understanding neural representation and the construction of accurate brain models. There are also potential medical benefits of an improved understanding of the role of hemodynamics in neural processing, as it directly bears on interpretation of and potential treatment for stroke, dementia, and epilepsy.
Address for reprint requests and other correspondence: C. I. Moore, MIT, McGovern Inst. for Brain Research, 46-2171, 77 Massachusetts Ave., Cambridge, MA 02139 (E-mail: cim{at}mit.edu )
Reference to glucocorticoids as "stress hormones" has been growing in prevalence in the literature, including in comparative and environmental endocrinology. Although glucocorticoids are elevated in ...response to a variety of stressors in vertebrate animals, the primary functions of glucocorticoids are not responding to stressors and they are only one component of complex suite of physiological and behavioral responses to stressors. Thus, the use of the short-hand phrase "stress hormone" can be misleading. Further, simply measuring glucocorticoids is not equivalent to measuring a stress response, nor is manipulating glucocorticoids equivalent to exposing an animal to a stressor. In this commentary we highlight the problems with using functional names for hormones, and of treating cortisol or corticosterone as synonymous with stress. We provide recommendations to add clarity to the presentation of research on this topic, and to avoid conflation of glucocorticoids with stressors and the stress response in the design of experiments.
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